A high HIF-1α expression genotype is associated with poor prognosis of upper aerodigestive tract carcinoma patients

Abstract

The aim of the present study was to evaluate the role of HIF-1α genetic polymorphisms and protein expression in the development of metastasis in upper aerodigestive tract cancer (UADTC) patients. The expression of pro-angiogenic markers was also evaluated. Protein expression was analysed using immunohistochemistry, and RFLP analysis was used to investigate HIF-1α C1779T and G1790A polymorphisms in 52 patients with UADTC. Primary lesions were divided into 2 groups according to the absence or presence of metastasis. Lymph node samples were divided into 3 groups: metastatic lymph nodes, non-metastatic lymph nodes (both derived from patients with metastatic disease), and control lymph nodes, which were obtained from patients without any metastasis. The allele T was more frequently found in patients with metastatic disease. HIF-1α protein expression in the lymph nodes was increased in the presence of the T allele. Metastatic lymph nodes showed lower levels of HIF-1α, VEGFR1, and MMP-9 proteins compared to lymph nodes without metastasis, while VEGFR2 protein levels were increased. In agreement, HIF-1α expression was correlated with MMP-9. Cox regression analysis demonstrated that higher HIF-1α and MMP-9 protein expression levels and GA and GG genotypes were associated with poor survival. Our findings show that the C1772T and G1790A polymorphisms of the HIF-1α gene are associated with increased expression of the HIF-1α protein in UADTC. The present data indicate that non-metastatic tissues express higher levels of HIF-1α, VEGFR1, and MMP-9, while in metastatic lymph nodes, VEGFR2 protein expression is elevated. The present study also shows that the HIF-1α G1790A polymorphism and its protein expression have an impact on the prognosis of UADTC patients.

Detection and quantification of mast cell, vascular endothelial growth factor, and microvessel density in human inflammatory periapical cysts and granulomas

“…However, the outcomes of the present study conflict with those of another comparative study that demonstrated a more MC staining with toluidine blue in granulomas compared with cysts (Marcal et al 2010). These mechanisms can change angiogenic proteins levels and consequently angiogenesis (Farias et al 2010, Fraga et al 2012. The present observations indicate that MCs could play an important role in the pathogenesis of chronic periapical lesions, more remarkably in cysts.…”

Metformin increases PDH and suppresses HIF-1α under hypoxic conditions and induces cell death in oral squamous cell carcinoma

“…Additionally, HIF1α increasing is related to worse prognoses of OSCC [21, 22]. Considering the role of PDH in OSCC, qRT-PCR was performed to compare PDH levels in patients with OSCC and patients with oral leukoplakia.…”

Analysis of p16_{<i>CDKN2A</i>} Methylation and HPV-16 Infection in Oral Mucosal Dysplasia

“…It is well known that exposure to smoking and ethylism for long periods are the principal causes of OSCC [1,30,31] . In the current study, age, smoking, and ethylism were associated with worse ED gradation.…”

“…karger.com/doi/10.1159/000334926). Tobacco smoking was classified according to our previous studies [1,30,31] . Ethical approval for this study was obtained from relevant local ethics committees (process No.…”

“…Paraffin sections (3 m) were mounted on glass and dried overnight at 37 ° C. The sections were incubated with anti-DNMT1, anti-DNMT3B (diluted 1: 250; Imgenex, San Diego, Calif., USA), or anti-P16CDKN2A clone JC8 (1: 500; Santa Cruz Biotechnology, Inc., Santa Cruz, Calif., USA) monoclonal antibodies at 4 ° C for 18 h. Next, we followed a previously described method [31] . Normal mucosa was used as a positive control, and the primary antibody was replaced with phosphate-buffered saline as a negative control.…”